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The function of Hes6 in myogenesis, rhabdomyosarcoma and neurogenesisMalone, Caroline Mary Patricia January 2011 (has links)
No description available.
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Étude de l'implication du système protéolytique neutre calcium-dépendant dans la migration des cellules musculaires tumoralesRoumes, Hélène 07 December 2009 (has links)
Les Rhabdomyosarcomes (RMS) sont des sarcomes qui touchent préférentiellement les enfants et les adolescents. Les RMS sont à l'origine de nombreuses métastases qui sont responsables d'une réduction importante de l'espérance de vie du malade. Une meilleure compréhension des mécanismes sous-tendant la migration et l'invasion des RMS pourrait orienter vers de nouvelles thérapies visant à enrayer le développement de métastases. La dissémination métastatique fait intervenir de nombreuses protéases dont la µ- et la m-calpaïne, cystéine-protéases, constituant avec leur inhibiteur endogène, la calpastatine, le système protéolytique neutre calcium-dépendant. Dans différents travaux, l'activité de ces calpaïnes a été montrée comme dérégulée, notamment dans le cancer du rein, de la peau ou encore les adénocarcinomes colorectaux. Une connaissance approfondie de l'impact de la dérégulation de l'activité des calpaïnes sur la dissémination métastatique pourrait en faire des cibles thérapeutiques de choix. L’étude de l’activité, de l’expression et de la localisation des différents composants du système protéolytique neutre calcium-dépendant a permis de mettre en évidence une activité dérégulée des calpaïnes dans les RMS. Cette forte activité serait due à une expression très faible de la calpastatine. L’analyse comparative des caractéristiques adhésives et cinétiques des RMS par rapport aux cellules témoins, des myoblastes humains (LHCN-M2) montre un faible taux d’adhésion associé à une vitesse de migration élevée des RMS. L’activité calpaïne présente une corrélation linéaire positive avec la vitesse de migration ; les calpaïnes se présentent donc comme marqueur de l’agressivité tumorale. L’inhibition des calpaïnes par la calpeptine réduit fortement cette vitesse. Le cytosquelette des RMS est désorganisé et ne présente pas, contrairement à celui des cellules non-tumorales, de fibres de stress. À ce niveau, les études pour tenter de discriminer le rôle de la µ-calpaïne et de la m-calpaïne, utilisant des oligonucléotides antisens, montrent que dans les LHCN-M2, la µ-calpaïne jouerait un rôle prépondérant dans la régulation de l’alpha-actine en régulant de manière négative son expression. Quant à la béta-actine, elle serait régulée, aussi de manière négative, mais, uniquement par la m-calpaïne. Dans les ARMS, la µ-calpaïne et la m-calpaïne jouent un rôle similaire en stimulant l’expression des deux isoformes. De plus, le pouvoir invasif important des RMS est fortement diminué lorsque l’activité calpaïne est inhibée. L’implication des calpaïnes tant au niveau de l’adhésion, de la migration que de l’invasion des RMS font de ces dernières une cible d’étude importante pour tenter de contrecarrer le développement de métastases. / Rhabdomyosarcoma (RMS) are a soft-tissue sarcoma commonly encountered in childhood and adolescence. RMS cells can acquire invasive behaviour and can form metastases which decrease less than 20% the patients healing. The comprehension of mechanisms that regulate cancer cells migration and invasion may be a key for development of new therapies for limiting metastasis. The metastatic dissemination implicates lots of proteases of which µ-calpain and m-calpain. Calpain activity is Ca2+-dependent and is principally regulated by calpastatin, its specific endogenous inhibitor. The deregulation of calpains has been involved in tumour invasion and metastasis in several different cell types. Then, calpains would be a good target for development of novel therapies to control metastasis. Study of calpain activity, expression, and localisation underline the deregulation of calpain activity in RMS. This high activity may be due to weak expression of calpastatin. The comparative analysis of adhesive and kinetical characteristics of RMS cells, compared to human myoblasts, LHCN-M2 cells, show a weak adhesiveness and an important migration velocity in RMS cells. The calpain activity presents a positive linear correlation with the migration velocity; so, calpain may be considered as marker of tumoral aggressiveness. The inhibition of calpain by calpeptin reduces significantly the migration velocity. The cytoskeleton RMS cells is disorganised and does not present stress fibers, contrary to LHCN-M2 cells. At this level, discrimination of µ- and m-calpain role, using antisens oligonucleotides, shows that in LHCN-M2 myoblasts, µ-calpain may negatively regulate the alpha-actin expression and that béta-actin may be positively regulated by the m-calpain. In ARMS cells, both µ- and m-calpain positively regulate alpha- and béta-actin. Moreover, the invasive behaviour of RMS cells is importantly decreased when calpains are inhibited. In summery, calpains may implicate in the anarchic adhesion, migration and increase of invasion. In this way, targeting calpain activity may represent a good strategy for limiting development of RMS tumour as well as their metastatic behaviour.
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Improving anti-tumor efficacy of low-dose Vincristine in rhabdomyosarcoma via the combination therapy with FOXM1 inhibitor RCM1Donovan, John 25 May 2023 (has links)
No description available.
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Role of RAS signaling in Hedgehog-associated embryonal rhabdomyosarcomaBauer, Julia 18 December 2018 (has links)
No description available.
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Eukaryotic Initiation Factor 2-associated glycoprotein P67 inhibits the tumorigenicity of Alveolar Rhabdomyosarcoma (ARMS) and involves its differentiation and migrationLiu, He 31 July 2019 (has links)
No description available.
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The role of LEF1 and WNT signaling in growth and differentiation of rhabdomyosarcomaDräger, Julia 02 February 2017 (has links)
No description available.
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Calculations of Radiobiological Treatment Outcome in RhabdomyosarcomaNyathi, Thulani 15 March 2007 (has links)
Thulani Nyathi, Student no: 0413256X, MSc thesis, Physics, Faculty of science. 2006. Supervisor: Prof D van der Merwe. / This study aims to calculate tumour control probabilities (TCP) and normal tissue
complication probabilities (NTCP) using radiobiological models and correlate these
probabilities with clinically observed treatment outcome from follow-up records. These
radiobiological calculations were applied retrospectively to thirty-nine paediatric patients
who were treated with radiation at Johannesburg Hospital during the period January 1990
to December 2000 and had histologically proven rhabdomyosarcoma. Computer
software, BIOPLAN, was used to calculate the TCP and NTCP arising from the dose
distribution calculated by the treatment planning system and characterized by dosevolume
histograms (DVHs).
There was a weak correlation between the calculated TCP and the observed 5-year
overall survival status.
Furthermore, potential prognostic factors for survival were examined. Statistical analysis
was performed using the Cox proportional hazards regression model. The 5-year overall
survival rate was 55 %. The findings of this study are a yardstick against which more
aggressive radiotherapy fractionation regimes can be compared.
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Disruption of Epigenetic Regulatory Elements and Chromosomal Alterations in Patients with Beckwith-Wiedemann SyndromeSmith, Adam Campbell 03 March 2010 (has links)
Genomic imprinting refers to the parent-of-origin specific monoallelic expression of a gene. Imprinted genes are often clustered in the genome and their expression is regulated by an imprinting centre (IC). ICs are regions of DNA that propagate the parental specific regulation of gene expression, which are usually characterized by differential DNA methylation, histone marks and the presence of non-coding RNAs. Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with the dysregulation of imprinted gene expression on human
chromosome band 11p15.5. The 11p15.5 imprinted region has two imprinting centres, IC1 and IC2. IC1 is telomeric and regulates the imprinted expression of the genes H19 and IGF2. IC2 is ~700kb centromeric and is associated with a cluster of nine imprinted genes including CDKN1C, KCNQ1 and an imprinted non-coding RNA associated with IC2, KCNQ1OT1. Loss of differential DNA methylation at IC2 is seen in 50% of patients with BWS with loss of
imprint of the non-coding RNA KCNQ1OT1 and associated with a decreased expression of the
putative tumour suppressor CDKN1C. Patients with BWS also have a thousand-fold increased
risk of pediatric cancer. The focus of this thesis involves investigation of dysregulation of
imprinting in three groups of BWS patients. Firstly, I show that BWS patients with alveolar
rhabdomyosarcoma have constitutional loss of methylation at IC2 and biallelic expression of
KCNQ1OT1. Secondly, loss of methylation at IC2 has been previously associated with female
monozygotic twins discordant for BWS. In male monozygotic twins with BWS, however, the
molecular lesions reflect the molecular heterogeneity seen in BWS singletons. Thirdly, BWS
patients associated with translocations and inversions that have breakpoints within the KCNQ1
gene near IC2 show regional gain of DNA methylation around the breakpoint and decreased
expression of CDKN1C. Therefore, using a rare collection of BWS patients, I have attempted to
determine the various roles of the imprinting centres IC1 and IC2 and their involvement in
tumourigenesis, monozygotic twinning and structural chromosomal rearrangements causing
BWS.
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Mechanisms of 4-hydroxytamoxifen-induced Apoptosis in Rhabdomyosarcoma CellsChen, Kevin Min 06 December 2011 (has links)
Rhabdomyosarcoma (RMS) is a malignant soft-tissue sarcoma in children, accounting for about 40% of pediatric soft-tissue tumours. Five-year survival for metastatic RMS is only about 25%. Furthermore, there has been no significant improvement in RMS survival since 1975, pointing to a need for improved therapy.
Previous work in our lab has shown that 4-hydroxytamoxifen (4OHT) leads to increased apoptosis and decreased viability in RMS cells. Expanding on this work, the current project aims to elucidate the mechanisms behind 4OHT-induced apoptosis in RMS cells, focusing on the roles of estrogen receptors (ER) and MAP kinases (MAPK).
We found that: 1) 4OHT-induced apoptotic signaling was associated with increased MAPK phosphorylation, 2) Inhibition of MAPK protected cells against 4OHT, 3) Inhibition of ER also protected against 4OHT, and 4) ER inhibition blocked 4OHT-associated MAPK phosphorylation.
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Mechanisms of 4-hydroxytamoxifen-induced Apoptosis in Rhabdomyosarcoma CellsChen, Kevin Min 06 December 2011 (has links)
Rhabdomyosarcoma (RMS) is a malignant soft-tissue sarcoma in children, accounting for about 40% of pediatric soft-tissue tumours. Five-year survival for metastatic RMS is only about 25%. Furthermore, there has been no significant improvement in RMS survival since 1975, pointing to a need for improved therapy.
Previous work in our lab has shown that 4-hydroxytamoxifen (4OHT) leads to increased apoptosis and decreased viability in RMS cells. Expanding on this work, the current project aims to elucidate the mechanisms behind 4OHT-induced apoptosis in RMS cells, focusing on the roles of estrogen receptors (ER) and MAP kinases (MAPK).
We found that: 1) 4OHT-induced apoptotic signaling was associated with increased MAPK phosphorylation, 2) Inhibition of MAPK protected cells against 4OHT, 3) Inhibition of ER also protected against 4OHT, and 4) ER inhibition blocked 4OHT-associated MAPK phosphorylation.
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